Delay discounting: effects of drug dependence and withdrawal

延迟折扣：药物依赖和戒断的影响

• 批准号: 8686803
• 负责人: CHARLES P FRANCE
• 金额: $ 27.19万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8686803
• 关键词: Acute; Adult; Affect; Agonist; Animals; Behavior; Behavioral; Benzodiazepines; Chronic; Data; Development; Diazepam; Dimensions; Dose; Drug Addiction; Drug abuse; Drug usage; Flunitrazepam; Grant; Heroin; Human; Impulsive Behavior; Impulsivity; Individual; Juice; Ketamine; Laboratories; Macaca mulatta; Measures; Mental disorders; Monkeys; Morphine; N-Methylaspartate; Opioid; Opioid Receptor; Oxymorphone; Pharmaceutical Preparations; Phencyclidine; Physical Dependence; Procedures; Relapse; Risk; Self Administration; Substance abuse problem; Testing; Time; Withdrawal; discounting; drug abuser; drug of abuse; drug withdrawal; high risk behavior; human data; indexing; male; non-drug; opioid withdrawal; prescription opioid; reinforcer; remifentanil; response; trait

DESCRIPTION (provided by applicant): Impulsivity, an increased tendency to act without thought or deliberation, is common in psychiatric disorders and often is observed in drug abusers. Although impulsivity might be a predisposing trait that contributes to the development of substance abuse, it might also be a result of drug use, thereby promoting ongoing abuse and possibly relapse. Studies have examined how acute administration of drugs affects impulsivity; however, most drug abuse involves repeated drug administration and often the development of physical dependence, yet few studies have examined how impulsivity is affected by chronic drug administration and its discontinuation. Impulsivity is multidimensional and several procedures have been developed for studying different but equally important dimensions of impulsivity; in one procedure, delay discounting, subjects choose between a smaller reinforcer that is delivered without delay and a larger reinforcer that is delivered after a delay. Increased responding for the smaller, immediately available reinforcer is thought to reflect greater impulsivity. Studies in this application examine effects of acute and chronic opioid treatment, and its discontinuation, on delay discounting in animals because in humans delay discounting is sensitive to opioid treatment and its discontinuation. Data from humans suggest that impulsivity contributes to drug abuse and that drug abuse increases impulsivity; delay discounting might also vary across different reinforcers (e.g., money versus drug). Proposed studies build on preliminary data showing that delay discounting is affected by daily administration of very small doses of morphine, suggesting that abuse of even small doses of drugs (e.g., prescription opioids) could significantly increase impulsivity. These studies examine how acute and chronic treatment with a prototypic 5 opioid receptor agonist (morphine), as well as discontinuation of treatment, impact delay discounting in adult male rhesus monkeys. Studies under AIM 1 build on preliminary studies and compare acute drug effects on delay discounting in monkeys responding for a non-drug reinforcer to effects in monkeys responding for a drug reinforcer; these studies test whether delay discounting is differentially altered when responding is maintained by different reinforcers and also test the pharmacologic selectively of these drug effects. Using the same monkeys, AIM 2 evaluates how chronic treatment with morphine and its discontinuation alter delay discounting under the non-drug and drug reinforced procedures; these studies examine the effects of daily treatment on delay discounting, whether tolerance develops to those effects, how discontinuation modifies delay discounting, and how the time course of changes in this measure of impulsivity correlates with indices of withdrawal. These studies examine the unexplored possibility that abuse of even small doses of opioids increases impulsivity that can be enduring; increased impulsivity might contribute to ongoing drug abuse, relapse, and other high risk behavior long after drug withdrawal is no longer evident.

描述（由申请人提供）：冲动性，不思考或审议的行动趋势增加，在精神疾病中很常见，并且在毒品滥用者中经常观察到。尽管冲动性可能是有助于滥用药物的诱人特征，但它也可能是吸毒的结果，从而促进了持续的滥用并可能复发。研究检查了药物的急性给药如何影响冲动。但是，大多数药物滥用涉及反复的药物管理，并且通常会发展身体依赖性，但是很少有研究研究了慢性药物管理及其中断的冲动性如何受到冲动的影响。冲动是多维的，已经开发了几种程序来研究不同但同样重要的冲动维度。在一个过程中，延迟打折，受试者在较小的增强器之间进行选择，该钢备会毫不延迟交付，而延迟后交付的较大的增强剂。人们认为，对较小的，立即可用的增强剂的响应增加被认为反映了更大的冲动性。在此应用中的研究检查了急性和慢性阿片类药物治疗的影响及其中断对动物延迟打折的延迟，因为在人类中，延迟打折对阿片类药物治疗及其停用敏感。来自人类的数据表明，冲动性有助于滥用药物，药物滥用增加了冲动性。延迟折现可能会因不同的增强剂而异（例如，货币与药物）。拟议的研究以初步数据为基础，表明延迟折现受每天给予非常小剂量的吗啡的影响，这表明滥用少量药物（例如，处方阿片类药物）的滥用可能会大大增加冲动性。这些研究检查了使用原型5阿片受体激动剂（吗啡）以及停用治疗的急性和慢性治疗，成年雄性恒河猴的损害延迟折现。 AIM 1的研究以初步研究为基础，并比较急性药物对降低猴子延迟打折的影响，这些猴子对非毒品增强剂做出了反应，以响应猴子对药物增强剂的响应；这些研究测试了不同的增强剂维持响应时延迟打折是否会差异化，并且还选择性地测试了这些药物作用的药理学。 AIM 2使用相同的猴子评估吗啡的慢性治疗方式及其中断如何在非药物和药物增强程序下改变延迟折现；这些研究检查了日常治疗对延迟打折的影响，对这些影响的容忍度是否发展，停用如何改变延迟折现，以及这种冲动性量度的变化时间与撤回指数相关。这些研究研究了未开发的可能性，即滥用少量阿片类药物会增加可能持久的冲动性。在不再显而易见的是，冲动性增加可能导致持续的滥用药物滥用，复发和其他高风险行为。